Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study.

BACKGROUND: Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. METHODS AND RESULTS: In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. CONCLUSIONS: The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.

ST 567 (alinidine) in stable angina: a comparison with metoprolol.

Alinidine, a drug which reduces heart rate without depressing myocardial function was compared against metoprolol, a beta-blocking drug, in the treatment of stable angina pectoris in a double-blind cross-over trial. It was found that both drugs reduced anginal attacks and nitroglycerine consumption to a comparable degree. Exercise tolerance did not appear to be improved by either drug yet chest pain at ergometry was postponed by both drugs. In the doses used metoprolol was more effective in restraining heart rate, both at rest and even more during exertion. Both drugs were well tolerated and side-effects were few. It seems probable that the optimal dose of alinidine was not used in this trial and that the dosage could have been higher.

Effect of continued rt-PA administration on the residual stenosis after initially successful recanalization in acute myocardial infarction--a quantitative coronary angiography study of a randomized trial.

Quantitative angiography was performed in 68 out of 123 patients treated with intravenous rt-PA for acute myocardial infarction. At 90 min angiography, the median minimal cross-sectional area was 1.11 mm2 and the median percentage area stenosis was 80%. A percentage area stenosis greater than 70% was seen in 78% of the patients. Patients with a patient infarct related artery at the first angiogram were randomized to receive subsequent infusions either of rt-PA + heparin or placebo + heparin. There was a persistent trend of improvement in minimal lumen diameter and percentage diameter stenosis of the residual stenosis in the infarct related artery in both treatment groups when re-examined 6-24 hours later and at the time of hospital discharge. A reduction in 'plaque area', the area between the detected and the reference contours of the infarct related segment, was more frequently seen in patients receiving a second infusion of rt-PA than in patients with no prolonged thrombolytic therapy (83% versus 57%, P less than 0.025, chi square).